scholarly journals Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chieko Kawakita ◽  
Koki Mise ◽  
Yasuhiro Onishi ◽  
Hitoshi Sugiyama ◽  
Michihiro Yoshida ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Lectin Binding ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Net Reclassification Improvement ◽  
Outcome Group ◽  
Lectin Array ◽  
Renal Prognosis ◽  
Glycan Profiling

AbstractIn IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11–7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11–4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(β1-4)GlcNAc and high-mannose including Man(α1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike’s information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.

scholarly journals Urinary Periostin Excretion Predicts Renal Outcome in IgA Nephropathy

2016 ◽  
Vol 44 (6) ◽  
pp. 481-492 ◽  
Author(s):  
Jin Ho Hwang ◽  
Jung Pyo Lee ◽  
Clara Tammy Kim ◽  
Seung Hee Yang ◽  
Jin Hyuk Kim ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Glomerular Sclerosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matricellular Protein ◽  
Tubular Atrophy ◽  
Renal Outcomes ◽  
Group 3

Background: Periostin is a matricellular protein and plays a vital role in tissue regeneration, fibrosis and wound healing. However, data about its significance in nephrology are limited. We investigated the correlation between urinary periostin excretion and its clinical significance including renal histologic findings and prognosis in IgA nephropathy (IgAN). Methods: Of 399 patients from a glomerulonephritis cohort recruited between January 2009 and December 2014, 314 were enrolled. Serum and urine periostin (uPOSTN) were measured using enzyme-linked immunosorbent assay. We divided the patients into 3 groups by uPOSTN/creatinine (uPOSTN/Cr): group 1 (undetectable), group 2 (lower than the median) and group 3 (higher than the median). Results: The uPOSTN level was correlated with pathologic classifications and both initial and final IDMS-MDRD estimated glomerular filtration rates (eGFRs; p < 0.001). Histologically, group 3 patients were correlated with severe interstitial fibrosis/tubular atrophy (p = 0.004), interstitial inflammation (p = 0.007), hyaline arteriolosclerosis (p = 0.001) and glomerular sclerosis (p < 0.001). A higher initial uPOSTN/Cr level was associated with a greater decline in eGFR during follow-up (p = 0.043 when initial eGFR ≥60; p = 0.025 when eGFR <60 ml/min/1.73 m2), and the renal outcomes with end-stage renal disease (ESRD; p = 0.003), ESRD and/or eGFR decrease of >30% (p = 0.033) and ESRD and/or eGFR decrease of >50% (p = 0.046) occurred significantly more in group 3. In multivariate analysis, uPOSTN group 3 (hazards ratio 2.839, 95% CI 1.013-7.957; p = 0.047) was independently associated with ESRD in IgAN patients. Conclusion: uPOSTN/Cr value at initial diagnosis correlated with renal fibrosis and predicted the renal outcomes in patients with IgAN. It could be a promising urinary biomarker for renal fibrosis.

scholarly journals Renal Outcome of IgM Nephropathy: A Comparative Prospective Cohort Study

2021 ◽  
Vol 10 (18) ◽  
pp. 4191
Author(s):  
Yura Chae ◽  
Hye Eun Yoon ◽  
Yoon Kyung Chang ◽  
Young Soo Kim ◽  
Hyung Wook Kim ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Immunoglobulin M ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Significant Difference ◽  
Lower Egfr ◽  
Matrix Expansion ◽  
Renal Prognosis

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN

scholarly journals The Correlation Analysis between the Oxford Classification of Chinese IgA Nephropathy Children and Renal Outcome -A retrospective cohort study

2019 ◽  
Author(s):  
Heyan Wu ◽  
Zhengkun Xia ◽  
Chunlin Gao ◽  
Pei Zhang ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iga Nephropathy ◽  
Interstitial Fibrosis ◽  
Cohort Analysis ◽  
Immunosuppressive Agents ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Independent Risk Factors

Abstract Background The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy, but it lacks large cohort validation in children with IgAN in China. We would like to verify that the MEST-C score can be used to predict the renal outcome of children with IgAN.Methods A retrospective cohort analysis of data from 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital from 2000 to 2017 was performed and investigated with glomerular filtration rate (eGFR),24h urine proteinuria(24h-UP)and blood pressure(BP) at biopsy and during follow-up.The renal pathology was based on Oxford Classification of IgAN.Results We confirm that BP was significantly correlated with mesangial hypercellullarity(M), endocapillary hypercellularity(E), tubular atrophy/ interstitial fibrosis(T) and crescents (C) .There was a significant correlation between eGFR and segmental glomerulosclerosis(S), T and C .24h-UP and all pathological indexes were significantly correlated. S and T were shown to be independent risk factors associated with renal outcomes in our group. Kaplan-Meier revealed that M [log-rank, chi-squared(χ2)=14.679, P=0.000 ], S(χ2=31.508,P=0.000),T (χ2=78.893, P=0.000),C(χ2=16.603, P=0.000) were associated with renal outcome.In univariate analyses, M(HR 2.167, 95% CI, 1.445~3.251, P = 0.000),S(HR 3.081, 95% CI, 2.038~4.658, P = 0.000), T(HR 7.911, 95% CI, 4.670~13.400,P = 0.000) and C(HR3.346, 95% CI, 1.818~6.156,P = 0.000) lesions were significant predictors of renal outcome. In a multivariate analysis, only S(HR 2.742, 95% CI, 1.805~4.164,P = 0.000) and T(HR 6.633, 95% CI, 3.897~11.289,P = 0.000)were shown to be independent risk factors .Conclusions We found that S and T lesions were valid in predicting a poor outcome in our group.E, S, T and C lesion were important basis for doctors to choose glucocorticoids and immunosuppressive agents in the treatment of IgAN, while T and C lesion were often the basis for doctors to use RAS blockers cautiously.

scholarly journals The Correlation Analysis between the Oxford Classification of Chinese IgA Nephropathy Children and Renal Outcome -A retrospective cohort study

2020 ◽  
Author(s):  
Heyan Wu ◽  
Zhengkun Xia ◽  
Chunlin Gao ◽  
Pei Zhang ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Iga Nephropathy ◽  
Retrospective Cohort Study ◽  
Cortical Area ◽  
Retrospective Cohort ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
The Oxford Classification

Abstract Background: The 2016 Oxford Classification's MEST-C scoring system predicts outcomes in adults with IgA nephropathy (IgAN), but it lacks large cohort validation in children with IgAN in China. We sought to verify whether the Oxford classification could be used to predict the renal outcome of children with IgAN. Methods : A total of 1243 Chinese children with IgAN who underwent renal biopsy in Jinling Hospital were enrolled from January 1, 2000, to December 31, 2017, in this retrospective cohort study. The primary endpoint of the study was a composite of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). We probed into the relationship between the Oxford classification and renal outcome. Results : There were 29% of children with mesangial proliferation(M1), 35% with endocapillary proliferation (E1), 37% with segmental sclerosis/adhesion lesion (S1), 23% with moderate tubular atrophy/interstitial fibrosis (T1 25–50% of cortical area involved), 4.3% with severe tubular atrophy/interstitial fibrosis (T2 >50% of cortical area involved), 44% with crescent in< 25% of glomeruli(C1), and 4.6% with crescent in>25% of glomeruli (C2).During a median follow-up duration of 7.2 (4.6–11.7) years, 171 children (14%) developed ESRD or 50% decline in eGFR. In the multivariate COX regression model, only segmental sclerosis/adhesion (HR2.7,95%CI 1.8～4.2, P ＜0.001) and tubular atrophy/interstitial fibrosis (HR6.6,95%CI 3.9～11.3, P ＜0.001) were confirmed to be independent risk factors of poor renal outcome in the whole cohort, whereas crescent showed significant association with prognosis only in children received no immunosuppressive treatment.Conclusions: This study revealed that segmental sclerosis/adhesion and tubular atrophy/interstitial fibrosis were independently associated with poor renal outcome in Chinese children with IgA nephropathy.

P0440EPIDEMIOLOGICAL AND CLINICAL CHARACTERSTICS OF IGA NEPHROPATHY PATIENTS IN TURKEY: TSN-GOLD WORKING GROUP

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Necmi Eren ◽  
Meltem Gursu ◽  
Egemen Cebeci ◽  
Aydin Turkmen ◽  
Hasan Haci Yeter ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Clinical Data ◽  
Working Group ◽  
Interstitial Fibrosis ◽  
Renal Outcome ◽  
Pathological Features ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Glomerular Diseases ◽  
Lower Egfr

Abstract Background and Aims According to the data of the Turkish Society of Nephrology-Glomerular Diseases Working Group (TSN-GOLD Working Group), IgA nephropathy is the most common primary glomerular disease in Turkey. The purpose of this study was to investigate the epidemiological and clinical data of IgA nephropathy patients in Turkey. Method 4399 patients with primary glomerular diseases from 47 centers who were followed up between May 2009 and May 2019 were included in the study conducted by TSN-GOLD Working Group. 524 patients were excluded due to lack of pathological data. Among the remaining patients, demographic, clinical and laboratory data of 994 patients with IgA nephropathy were analyzed. Results The median age of the patients was 37 (28-47) years, and 37.3% of them were female. The laboratory and clinical data at the time of diagnosis is presented in Figure-1, and biopsy indications are described in Figure-2. The median number of glomeruli was 16 (IQR: 3.5-4.3), sclerotic glomeruli was 2 (IQR: 1-5), and segmental sclerotic glomeruli was 1 (IQR: 1-2). Exudative changes, subendothelial and subepithelial deposition were present in 566 patients (56.9%), 46 patients (4.6%) and in 38 patients (3.8%), respectively. 662 (66.1%) and 611 of the patients (61.4%) had tubular atrophy and interstitial fibrosis in varying degrees, respectively. 672 (%67.6) and 416 patients (%41.9) had interstitial inflammation and vascular changes, respectively. In immunofluorescence staining, 18%, 30.1%, 4.4%, 68% of the patients had IgG, IgM, C1q and C3 positivity, respectively. Crescentic glomeruli were detected in 227 patients (3.3 ± 3.1 glomeruli). Patients with crescentic glomeruli had significantly higher proteinuria and lower eGFR than the patients without [2203 mg/day (15-26078) vs 1807 mg/day (15-29112); p=0.001; 55.3 ml/min/1.73 m2 (3.72-141.9) vs 72 ml/min/1.73 m2 (3.84-150.81); p&lt;0.001, respectively]. Oxford classification was applied to 544 patients. Endocapillary hypercellularity (E1), mesengial hypercellularity (M1), tubular atrophy and interstitial fibrosis (T1 and T2), segmental sclerosis (S1) were present in 126 (13%), 425 (42.8%), 306 (30.8%) and 325 patients (%32.7), respectively. Proteinuria levels were higher in patients with endocapillary hypertrophy, mesengial hypercellularity, tubular atrophy-interstitial fibrosis and segmental sclerosis. eGFR levels were lower in patients with endocapillary hypertrophy, tubular atrophy-interstitial fibrosis and segmental sclerosis (Figure-3). Conclusion In this study we found that, the most common presentation of IgA nephropathy patients in our country was asymptomatic urinary abnormalities followed by nephritic and nephrotic syndrome. Higher proteinuria and lower eGFR values in patients with crescentic glomeruli, support the adoption of crescentic lesions in the new Oxford classification (MEST-C) to predict more precise outcome of IgA nephropathy patients. The high number of patients to whom the Oxford classification was applied provided us with the opportunity to examine the clinical reflections of pathological features. Evaluation of the follow-up data of the patients will give us the possibility to reveal the effect of initial clinical and pathological features on clinical findings and renal outcome.

scholarly journals The Relationship between Cigarette Smoking and IgA Nephropathy

2021 ◽  
Author(s):  
Siqing Wang ◽  
Aiya Qin ◽  
Gaiqin Pei ◽  
Zheng Jiang ◽  
Lingqiu Dong ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Renal Outcome ◽  
Study Endpoint ◽  
Tubular Atrophy ◽  
Cox Regression Analysis

Abstract Background and aim: Regarding that whether cigarette smoking is associated with the progression of IgA nephropathy (IgAN) remains uncertain, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN.Methods: 1239 IgAN patients who meet inclusion criteria from West China Hospital of Sichuan University were divided into smoker and non-smoker group. The endpoint was end stage renal disease (ESRD: eGFR <15 mL/min/1.73 m2 or having renal replacement treatment) and/or eGFR decreased>50%. Kaplan-Meier and Cox proportional hazards analyses were performed. Association of cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis.Results: During the mean follow-up period of 61 months, 40 out of 209 (19%) patients in smoker group and 110 out of 1030 (11%) in non-smoker group reached study endpoint(p<0.001). Multivariate Cox regression analysis revealed that cigarette smoking (HR=1.58,p=0.043), female gender (HR=2.00,p=0.002), Hypertension (HR=1.50,p=0.029), Serum creatinine (HR=1.01,p<0.001), segmental glomerulosclerosis (HR=1.59,p=0.026), and tubular atrophy/interstitial fibrosis (HR=3.13,p<0.001) were independent risk factors for prediction of poor renal outcome of IgAN. After matching with propensity scores, the significant correlation between cigarette smoking and the renal outcomes of IgAN patients can be seen.Conclusion: Smoking is an independent risk factor for the progression of IgAN, especially for female subjects.

scholarly journals Is mycophenolate mofetil combined with low-dose prednisone a treatment option for advanced IgA nephropathy? A 10-year follow-up case and brief literature review

2018 ◽  
Vol 16 ◽  
pp. 205873921880268
Author(s):  
Qijun Wan ◽  
Yongcheng He ◽  
Hongtao Chen ◽  
Hongping Liu ◽  
Saodong Luan ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Iga Nephropathy ◽  
Treatment Option ◽  
Low Dose ◽  
Interstitial Fibrosis ◽  
Immunosuppressive Treatment ◽  
Channel Blockers ◽  
Tubular Atrophy ◽  
Dose Prednisone

IgA nephropathy (IgAN) is now widely recognized as the most common primary glomerulonephritis worldwide, especially in China. The immunosuppressive treatment option for IgAN is still controversial. Previously, we proved that mycophenolate mofetil (MMF; Shanghai Roche, China) combined with low-dose prednisone was an effective and safe option for biopsy-proven mild to moderate IgAN patients in a short term of follow-up. This article we first reported the safety and efficacy of this regimen in a 42-year-old male biopsy-proven advanced 10-year follow-up IgAN case (Lee’s Class V; the patient was biopsied 10 years ago, so the Oxford Mesangial hypercellularity Endocapillary hypercellularity Segmental glomerulosclerosis Tubular atrophy/interstitial fibrosis (MEST) classification was not used). The mycophenolate and prednisone were only given for a limited time. The other main medications included calcium channel blockers and antiplatelet agents. Clinical and laboratory indexes were aperiodic assessed during the 10-year follow-up. The serum creatinine decreased from 356 to around 210 μmol/L and urine excretion protein reduced from 3.4 g/d to about 0.5 g/d after 6 months of the initiation of this regimen, respectively. These perfect treatment effects could maintain well during the whole follow-up period. No obvious complications were observed.

scholarly journals Clinicopathologic Features of Infection-Related Glomerulonephritis with IgA Deposits: a French Nationwide Study

2020 ◽  
Author(s):  
Elodie Miquelestorena-Standley ◽  
Charlotte Jaulerry ◽  
Marie-Christine Machet ◽  
Nolwenn Rabot ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Outcome Data ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Short Delay ◽  
Adult Men ◽  
Staphylococcus Infections ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results: Twenty-seven patients (23 men, mean age: 62±15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of >4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

scholarly journals Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Coagulation System ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Tubular Atrophy ◽  
Coagulation Parameters ◽  
T Score ◽  
Stage Renal Disease

Abstract Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods: This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s). Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

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